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Blood, 15 October 2007, Vol. 110, No. 8, pp. 3082.
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CORRESPONDENCE
Extracellular localization of epimorphin/syntaxin-2
To the editor:
In a recent article, Flaumenhaft et al1 showed that syntaxin-2 is found on the extracellular cell surface on activated platelets. While they conclude that theirs is the first demonstration of extracellular presentation of a syntaxin molecule, it should be noted that the syntaxin-2 protein is identical to epimorphin, which was identified first in 1992 as an extracellular morphogen through the use of function-blocking antibodies in lung and skin organ culture assays2 and then in 1993 renamed as syntaxin-2, a member of the SNARE family of proteins that mediates intracellular vesicle fusion.3 As an extracellular morphogen, epimorphin has been found to be associated with the extracellular cell surface and also as a secreted molecule, acting to influence developmental processes of a wide variety of tissues including lung, mammary gland, liver, intestine, pancreas, cartilage, and hair follicle.2,4–8
The function of platelet cell surface epimiorphin/syntaxin-2 is unclear. In the cytoplasm, epimorphin/syntaxin-2 is localized to the inner surface of the plasma membrane as a target SNARE (t-SNARE) and acts to mediate fusion with vesicles that possess the appropriate vesicle SNARE (v-SNARE) proteins.9 Flaumenhaft et al1 suggest that platelet cell surface epimorphin/syntaxin-2 may play a role analogous with its intracellular function, perhaps by mediating cell-cell fusion events. To accomplish this, the target cells would also need to present extracellular v-SNARE proteins and, to date, there are no indications for extracellular presentation of v-SNARE proteins. Another possibility is that platelet cell surface epimorphin/syntaxin-2 may function as an adhesive or signaling molecule, as it functions in many other cell types.2,4–7 Epimorphin/syntaxin-2 has been found to bind  Vß5 and Vß1 integrins on target epithelial cells and to initiate specific signaling processes10; platelet cell surface epimorphin may similarly facilitate adhesion and/or cell signaling processes with endothelial or other cell types through association with cell surface integrins on these target cells. In either case, the recent studies of Flaumenhaft et al are a key first step in the elucidation of platelet-specific functions controlled by this intriguing molecule.
Authorship
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Yohei Hirai, Department of Morphoregulation, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; e-mail: hirai-yohei{at}frontier.kyoto-u.ac.jp.
Yohei Hirai,
Mina J. Bissell, and
Derek C. Radisky
References
- Flaumenhaft R, Rozenvayn N, Feng D, Dvorak AM. SNAP-23 and syntaxin-2 localize to the extracellular surface of the platelet plasma membrane. Blood 2007; 110:1492–1501.[Abstract/Free Full Text]
- Hirai Y, Takebe K, Takashina M, Kobayashi S, Takeichi M. Epimorphin: a mesenchymal protein essential for epithelial morphogenesis. Cell 1992; 69:471–481.[CrossRef][Medline]
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- Bennett MK, Garcia-Arraras JE, Elferink LA, et al. The syntaxin family of vesicular transport receptors. Cell 1993; 74:863–873.[CrossRef][Medline]
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- Iizuka M, Sasaki K, Hirai Y, et al. Morphogenic protein epimorphin protects intestinal epithelial cells from oxidative stress by the activation of EGF receptor and MEK/ERK, PI3 kinase/Akt signals. Am J Physiol Gastrointest Liver Physiol 2007; 292:G39–G52.[Abstract/Free Full Text]
- Oka Y, Sato Y, Tsuda H, Hanaoka K, Hirai Y, Takahashi Y. Epimorphin acts extracellularly to promote cell sorting and aggregation during the condensation of vertebral cartilage. Dev Biol 2006; 291:25–37.[CrossRef][Medline]
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- Radisky DC, Hirai Y, Bissell MJ. Delivering the message: epimorphin and mammary epithelial morphogenesis. Trends Cell Biol 2003; 13:426–434.[CrossRef][Medline]
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- Takebe K, Oka Y, Radisky D, et al. Epimorphin acts to induce hair follicle anagen in C57BL/6 mice. FASEB J 2003; 17:2037–2047.[Abstract/Free Full Text]
- Hirai Y, Radisky D, Boudreau R, et al. Epimorphin mediates mammary luminal morphogenesis through control of C/EBPbeta. J Cell Biol 2001; 153:785–794.[Abstract/Free Full Text]
- Jahn R and Scheller RH. SNAREs: engines for membrane fusion. Nat Rev Mol Cell Biol 2006; 7:631–643.[CrossRef][Medline]
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- Hirai Y, Nelson CM, Yamazaki K, et al. Non-classical export of epimorphin and its adhesion to {alpha}v-integrin in regulation of epithelial morphogenesis. J Cell Sci 2007; 120:2032–2043.[Abstract/Free Full Text]
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